Safety, efficacy, and pharmacokinetics of intravenous busulfan in children undergoing allogeneic hematopoietic stem cell transplantation

Donna A. Wall, Ka Wah Chan, Michael L. Nieder, Robert J. Hayashi, Andrew M. Yeager, Richard Kadota, Donna Przepiorka, Khaled Mezzi, Morris Kletzel

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Purpose. To determine the safety, efficacy, and PK profile of intravenous busulfan (Bu) in the context of a Bu and cyclophosphamide (IVBuCy) preparative regimen in children undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Methods. Twenty-four children were enrolled in an open-label, multicenter trial of IVBuCy as the preparative regimen for HLA-matched sibling allogeneic HSCT. IVBu was administered q6 hr for 16 doses with a targeted area under the curve (AUC) of 900-1,350 μMol-min. The initial dose was 0.8 mg/kg for children >4 years of age and 1 mg/kg for those <4 years of age. PK of the first dose IVBu was determined to calculate a single dosage adjustment, and with the 9th and 13th doses to confirm steady-state PK. Results. The targeted AUC was achieved with the first dose in 17/ 24 (71%) of the children using the age-adjusted dosing approach. Dosing was increased in five patients, and reduced in two patients to achieve target values. After dose adjustment based on PK, 91% of the children had an AUC within the target range at steady state (AUCss). Median final dosing and clearance (CL) of IVBu were 1.1 mg/kg and 4.1 ml/min/kg in patients <4 years, and 0.9 mg/kg and 2.9 ml/min/kg in patients >4 years. All children were engrafted with documented donor chimerism. No late rejections or graft failures occurred. Four patients had veno-occlusive disease, three of which resolved within 2 weeks of onset. Two children died from transplantrelated causes unrelated to Bu. Conclusion. IVBu is a safe and effective and offers the benefit of predictable and consistent systemic exposure.

Original languageEnglish (US)
Pages (from-to)291-298
Number of pages8
JournalPediatric Blood and Cancer
Volume54
Issue number2
DOIs
StatePublished - Feb 2010

Keywords

  • Bone marrow transplantation
  • Children
  • Hematopoietic stem cell transplantation
  • Intravenous busulfan
  • Pharmacokinetics

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

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